Acetaminophen(APAP)is the most wideIy-used anaIgesic drug cIinicaIIy. It is aIso the most risky agent for hepatotoxicity. It has been wideIy used as a modeI drug to study mechanisms of chemicaI-induced Iiver injury and to test the hepatoprotective potentiaI of chemicaIs. This review summa-rized the intraceIIuIar events of acetaminophen-induced hepatotoxicity,incIuding metaboIic activation, ceIIuIar damage,c-Hun N-terminaI kinase pathway,and modified metaboIism function,and additionaIIy focused on the roIe of infIammatory factors and ceIIs in APAP hepatotoxicity,as weII as protection strate-gies of chemicaIs and naturaI products.